During the treatment with E. coli L-asparaginase in one adult and one child patient with acute myeloid leukemia, severe cerebral signs of toxicity, such as apathy, lethargy, confusion, and coma have been observed.
The necropsy findings of the brain are bilateral demyelating lesions of the cerebellum in the adult case and of the thalamus in the child patient.
Liver toxicity has been evident both in terms of function tests—serum bilirubin, SGOT, SGPT, LDH, and morphological changes—fatty metamorphosis and necrosis.
A correlation between these abnormalities and elevated blood ammonia levels has been suggested, and a resemblance of these changes to the pseudoulegyric type of hepatocerebral disease has been discussed.
L-asparaginase as a last choice of antileukemic drugs should be used most carefully with a countermeasure for its side effects.

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This paper deals with the results of 27 cases (16 myelogenous, 5 monocytic, 5 lymphogenous and 1 case with erythroleukemia) of acute leukemia with a new anti-leukemic agent “Neocarzinostatin”. It was administered alone in 14 cases, concomitantly with prednisolone 10∼80 mg/day in 9 cases and with prednisolone, 6 MP 100 mg/day and cyclocytidine 300∼500 mg/day in 4 cases. A course of Neocarzinostatin administration was 0.04∼0.06 mg/kg/day daily for 2∼5 days by intravenous perfusion.
A complete remission was obtained in 7 of 14 cases (50.0%) treated with Neocarzinostatin alone, 2 of 9 cases (22.2%) treated with Neocarzinostatin and prednisolone and 1 of 4 cases (25.0%) treated with Neocarzinostatin, prednisolone, 6 MP and cyclocytidine.
It is noteworthy that the treatment of Neocarzinostatin alone or combination with prednisolone induced a complete remission in 5 of 8 cases (62.5%) in the groupe of age over 50 year old. A potent leukemocidal effect was proved in most of all cases which have not been induced a remission. Clinically Neocarzinostatin had no cross-resistance with 6 MP and prednisolone.
Side effect of Neocarzinostatin such as nausea and vomiting was not so severe to stop the drug. The degree of myelosupression with Neocarzinostatin was severe, but it was mild when the dosage was reduced to 0.04 mg/kg/day.
From these data Neocarzinostatin was considered to be a new excellent antileukemic agent.

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Dibromomannitol, a halogenated polyalcohol, used orally was found to be effective in the treatment of chronic myelogenous leukemia. In 9 patients with chronic myelogenous leukemia, dibromomannitol was administered in a single daily dose of 250 mg for remission induction, this later decreasing to a dose ranging from 50 mg to 250 mg q. d. or q. o. d. for remission maintenance. The dose was adjusted according to peripheral blood counts while in remission. of/4 courses of treatment in them, symptomatic and hematologic control was achieved in/3 courses (93%) by 9 weeks (median). Regardless of previous treatment, high resoonce rate to this drug was obtained, suggesting the efficacy of dibromomannitol in patients resistent to other conventional cytotoxic drug.
The myelosupression was, within the dose range employed, relatively granuloytespecific. Side effect was minimal, such as mild gastrointestinal disturbance.

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Three brothers out of four had the same symptoms as “Familial erythroid multinuclearity” (reported by Wolff & Von Hofe, 1951) and as “Familial abnormality of the nucleus of the erythroblasts” (reported by Kosaka et al., 1958). The three brothers had abnormality of the nucleus of the erythroblasts. The youngest two were twins. One suffered from the disease, while the other is still in good health.
From the hematological point of view the disease is characterized by moderate macrocytic hyperchromic anemia, the appearance of megaloblastoid cells in the bone marrow and the abnormality of the nucleus of the erythroblasts.
These three cases were all premature babies with chronic diarrhea, malnutrition and mental disturbances. In addition, they were susceptible to infectious diseases, especially to viral ones. Two cases of these three died of varicella. The other was cured at last, though suffered from serious varicella. But finally he had to die after suffering from pneumonia four times. The process of the disease mentioned above were quite different from that of other cases reported in the past.

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Purpura hyperglobulinemica is relatively rare disease and only 27 cases were reported in Japan.
It attracted considerable attention because of its possible relationship to the more common diseases associated with γ-globulin alteration.
The present report concerns a case of purpura hyperglobulinemica which appeared to have developed after chronic pulmonary infection with bronchiectasis.
A 12 year-old-girl with abnormal lung shadow on chest X-ray film had purpura on both lower extremities and hematuria. Hilar shadow and streaky infiltration of the left lower lung were found in 1965 when she was 6 yrs old, without any signs of pneumonica. She had been treated as pulmonary tuberculosis, but PPD test was always negative and tuberculous bacilli were not detected. In September, 1968, purpura on the lower extremities and hematuria appeared. As they persisted and gradually increased, she was referred to our hospital in September 1970. Bronchography showed a marked bronchiectasis of the left lower lung.
The relevant laboratory findings are summerized as below: total serum protein 9.0 g/100ml, γ-globulin 40.6%, RF positive, cryoglobulin positive, Coombs' test positive, but analytical ultracentrifugation sudies did not reveal any intermediate complex between 7S and 19S components. From those results and clinical picture the patient was diagnosed as purpura hyperglobulinemica followed chronic pulmonary infection. Total resection of the left lung was done in November, 1971. After the removal of the infection site, serum γ-globulin and RF titer decreased and CRP test, Coombs' test and cryoglobulin tended to be negative. At the same time purpura disappeared and clinical picture improved markedly.

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A 48-year-old housewife was admitted because of dyspnea, hemorrhagic tendency and severe pains of lower limbs. Hematologic examinations showed severe anemia, thrombocytopenia and leukocytosis with atypical myeloblasts and promyelocytes. A bone marrow specimen revealed a high percentage of leukemic myeloblasts and promyelocytes. The chest X-ray showed marked pleural effusions containing numerous mononuclear cells which had the identical karyotype with leukemic cells in marrow (45, XX, C-, Cq-, D+, G-). A complete remission of five months was induced by combination therapy with prednisolone, 6-mercaptopurine, methotrexate and vincristine, and pleural effusions disappeared completely. Then, relapse occurred with pleural effusions and complete transverse spinal palsy at the 7 th thoracic segment developed suddenly, and the patient died nine months after admission. The postmortem examinations disclosed many tumors composed of leukemic cells, particularly in the dura mater of the spinal cord and bilateral pleurae.

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The present communication deals with 2 cases of pregnancy in leukemic patients.
The first case was a 22 year-old woman with acute myeloblastic leukemia, who had been treated with blood transfusion, corticosteroid and 6 MP for about one year. The patient was then noticed to have pregnanted. This was terminated by therapeutic abortion at 2nd month of her pregnancy. She recovered from this abortion uneventfully.
The second case was a 30 year-old woman with 5th month of her pregnancy. Chronic myelogenous leukemia was found at the routine check up. She had continued her pregnancy without receiving any treatment for leukemia. A normal healthy baby was born with a full-term normal delivery. However, severe vaginal bleeding occured following the delivery and supravaginal amputation was necessary to control this haemorrhage. The patient has then been treated with carbazilquinone and has been well up-to the present. The baby is now 5 month-old and enjoying his good health.
Pregnancy in the patient with leukemia is not uncommon. In Japan 61 cases have been reported including the present 2 cases: 45 with acute leukemia, 14 with chronic leukemia, and 2 with erythroleukemia.
These 61 cases were analized and the problems of pregnancy in the patients with leukemia were discussed from the following viewpoints;
1) frequency
2) influence of leukemia on pregnancy and delivery
3) effect of pregnancy and delivery on leukemia
4) abortion or maintenance of pregnancy
5) influence of leukemia on the fetus

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